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1zv8

From Proteopedia

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[[Image:1zv8.gif|left|200px]]<br /><applet load="1zv8" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1zv8, resolution 1.94&Aring;" />
 
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'''A structure-based mechanism of SARS virus membrane fusion'''<br />
 
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==Overview==
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==A structure-based mechanism of SARS virus membrane fusion==
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Entry of SARS coronavirus into its target cell requires large-scale structural transitions in the viral spike (S) glycoprotein in order to induce fusion of the virus and cell membranes. Here we describe the identification and crystal structures of four distinct alpha-helical domains derived from the highly conserved heptad-repeat (HR) regions of the S2 fusion subunit. The four domains are an antiparallel four-stranded coiled coil, a parallel trimeric coiled coil, a four-helix bundle, and a six-helix bundle that is likely the final fusogenic form of the protein. When considered together, the structural and thermodynamic features of the four domains suggest a possible mechanism whereby the HR regions, initially sequestered in the native S glycoprotein spike, are released and refold sequentially to promote membrane fusion. Our results provide a structural framework for understanding the control of membrane fusion and should guide efforts to intervene in the SARS coronavirus entry process.
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<StructureSection load='1zv8' size='340' side='right'caption='[[1zv8]], [[Resolution|resolution]] 1.94&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1zv8]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome-related_coronavirus Severe acute respiratory syndrome-related coronavirus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZV8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ZV8 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.94&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CAC:CACODYLATE+ION'>CAC</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1zv8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1zv8 OCA], [https://pdbe.org/1zv8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1zv8 RCSB], [https://www.ebi.ac.uk/pdbsum/1zv8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1zv8 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/SPIKE_SARS SPIKE_SARS] May down-regulate host tetherin (BST2) by lysosomal degradation, thereby counteracting its antiviral activity.<ref>PMID:31199522</ref> Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Binding to human ACE2 and CLEC4M/DC-SIGNR receptors and internalization of the virus into the endosomes of the host cell induces conformational changes in the S glycoprotein. Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membrane fusion within endosomes.[HAMAP-Rule:MF_04099]<ref>PMID:14670965</ref> <ref>PMID:15496474</ref> Mediates fusion of the virion and cellular membranes by acting as a class I viral fusion protein. Under the current model, the protein has at least three conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes.[HAMAP-Rule:MF_04099] Acts as a viral fusion peptide which is unmasked following S2 cleavage occurring upon virus endocytosis.[HAMAP-Rule:MF_04099]<ref>PMID:19321428</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/zv/1zv8_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1zv8 ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1ZV8 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Human_sars_coronavirus Human sars coronavirus] and [http://en.wikipedia.org/wiki/Sars_coronavirus Sars coronavirus] with <scene name='pdbligand=CAC:'>CAC</scene>, <scene name='pdbligand=ACT:'>ACT</scene>, <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=NA:'>NA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZV8 OCA].
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*[[Sandbox 3001|Sandbox 3001]]
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*[[Spike protein 3D structures|Spike protein 3D structures]]
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==Reference==
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== References ==
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Structures and polymorphic interactions of two heptad-repeat regions of the SARS virus S2 protein., Deng Y, Liu J, Zheng Q, Yong W, Lu M, Structure. 2006 May;14(5):889-99. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16698550 16698550]
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<references/>
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[[Category: Human sars coronavirus]]
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__TOC__
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[[Category: Protein complex]]
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</StructureSection>
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[[Category: Sars coronavirus]]
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[[Category: Large Structures]]
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[[Category: Dai, J.]]
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[[Category: Severe acute respiratory syndrome-related coronavirus]]
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[[Category: Deng, Y.]]
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[[Category: Dai J]]
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[[Category: Liu, J.]]
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[[Category: Deng Y]]
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[[Category: Lu, M.]]
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[[Category: Liu J]]
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[[Category: Yong, W.]]
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[[Category: Lu M]]
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[[Category: Zheng, Q.]]
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[[Category: Yong W]]
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[[Category: ACT]]
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[[Category: Zheng Q]]
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[[Category: CAC]]
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[[Category: NA]]
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[[Category: ZN]]
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[[Category: coiled coils]]
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[[Category: conformational change]]
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[[Category: membrane fusion]]
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[[Category: s2]]
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[[Category: sars coronavirus]]
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[[Category: virus entry]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:19:23 2008''
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Current revision

A structure-based mechanism of SARS virus membrane fusion

PDB ID 1zv8

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